Photodynamic therapy (PDT) is a cancer treatment modality that has shown promising results in terms of selectivity and efficacy, see e.g. Dougherty T J, et. al.: Photodynamic therapy, Journal of the National Cancer Institute 1998; 90: 889-905.
PDT relies on the use of a photosensitizer agent being activated by light in the presence of oxygen, leading to the production of toxic singlet oxygen radicals. Tissue destruction results from apoptosis, necrosis and vascular damage caused by these toxic singlet oxygen radicals, see e.g. Noodt B B, et. al.: Apoptosis and necrosis induced with light and 5-aminolaevulinic acid-derived protoporphyrin IX, British Journal of Cancer 1996; 74: 22-29.
A limited penetration in the tissue of the activating light is a general issue of PDT. Only tumors less than about 5 mm in thickness may be treated by surface irradiation. In order to treat thicker and/or deeper lying tumors, interstitial PDT may be utilized. In interstitial PDT, light-conducting optical fibers are brought into the tumor using, e.g., a syringe needle, in the lumen of which a fiber has been placed, which is for instance described in PCT/SE2006/050120 of the same applicant as the present application.
In order to achieve an efficient treatment, several fibers have been used to ascertain that all tumor cells are subjected to a sufficient dose of radiation so that the toxic singlet state is obtained. In the Swedish patent SE 503408 an interstitial PDT system is described, where six fibers are used for treatment as well as for measurement of the light flux which reaches a given fiber in the penetration through the tissue from the other fibers. According to the disclosure of SE 503408, the light from a single laser is divided into six different parts using a beamsplitter system comprising a large number of mechanical and optical components. The light is then focused into each of the six individual treatment fibers. One fiber is used as a transmitter while the other fibers are used as receivers of radiation penetrating the tissue. The interstitial PDT system disclosed in SE503408 allows feedback from light scattering but the document does not disclose any information or gives guidance concerning parameters of importance for controlling and adjusting light therapy or a need therefor.
To optimize the biological effect in interstitial PDT, an accurate dosimetry method is needed. For instance a fixed light dose may be used, and radiance at a therapeutic wavelength of the therapeutic light used may be kept constant throughout the PDT treatment. Furthermore, the illumination time may be determined by a requirement to deliver a pre-determined incident light dose, expressed in J/cm2. Such a simplified dose metric ignores changes of treatment conditions during PDT treatment. For instance, such changes may comprise treatment-induced variations of tissue light transmission, variations of sensitizer concentration, and varying tissue oxygenation status throughout the target tissue to be treated by PDT. Amongst other things, such variations might explain the highly variable PDT effect observed. For instance a recurrence rate displays large variations despite equivalent light dose, as shown in Calzavara-Pinton PG: Repetitive photodynamic therapy with topical α-aminolaevulinic acid as an appropriate approach to the routine treatment of superficial non-melanoma skin tumors, Journal of Photochemistry and Photobiology B: Biology 1995; 29: 53-57. Moreover, necrotic volume displays large variations despite equivalent light dose, according to Curnow A et. al.: Oxygen monitoring during 5-aminolaevulinic acid induced photodynamic therapy in normal rat colon, Comparison of continuous and fractionated light regimes, Journal of Photochemistry and Photobiology B: Biology 2000; 58: 149-155.
EP 1470837 of Tulip et. al. discloses a switched photodynamic therapy apparatus and method. A photodynamic therapy apparatus and method are described in which a phototoxic drug is supplied to an arterical supply of a target tissue, and delivery of drug activating light to target tissue through probes is controlled by sequential selection of operation of the probes. Furthermore, an automatic radiance probe is used for efficient optical characterization of target tissue and optical dose is monitored by sequential selection of probes as transmitters and receivers. However, the apparatus and method are not providing an efficiency feedback of the therapy delivered. Furthermore, the disclosure lacks a practical guidance of how and when to control light delivery as the probes are operated sequentially at a fixed, predetermined rate. Moreover, a specific rotational probe has to be used for measuring tissue characteristics of a treatment site, which appears practically difficult to implement in a clinical environment.
Hence, there is a need for an advantageous method and/or system for controlling and adjusting light therapy and/or related parameters during PDT in vivo or in vitro.